HEXIM1

Summary

HEXIM1 (HEXIM P-TEFb complex subunit 1, HGNC:24953) is a protein-coding gene on chromosome 17q21.31, encoding Protein HEXIM1 (O94992). Transcriptional regulator which functions as a general RNA polymerase II transcription inhibitor. It is a selective cancer dependency (DepMap: 22.4% of cell lines).

Expression of this gene is induced by hexamethylene-bis-acetamide in vascular smooth muscle cells. This gene has no introns.

Source: NCBI Gene 10614 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 38 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 22.4% of screened cell lines
• MANE Select transcript: NM_006460

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24953
Approved symbol	HEXIM1
Name	HEXIM P-TEFb complex subunit 1
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	CLP-1, HIS1, MAQ1, EDG1
Ensembl gene	ENSG00000186834
Ensembl biotype	protein_coding
OMIM	607328
Entrez	10614

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000332499

RefSeq mRNA: 1 — MANE Select: NM_006460 NM_006460

CCDS: CCDS11495

Canonical transcript exons

ENST00000332499 — 1 exons

Exon	Start	End
ENSE00001336971	45148475	45152099

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 95.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.6674 / max 740.5761, expressed in 1810 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161236	20.1122	1796
161238	1.7493	921
161240	1.2972	791
161237	1.1108	752
161239	0.2046	73
161241	0.1933	69

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	95.99	gold quality
granulocyte	CL:0000094	95.67	gold quality
gingival epithelium	UBERON:0001949	95.41	gold quality
middle temporal gyrus	UBERON:0002771	95.41	gold quality
germinal epithelium of ovary	UBERON:0001304	95.24	gold quality
nephron tubule	UBERON:0001231	95.16	gold quality
renal glomerulus	UBERON:0000074	95.08	gold quality
epithelium of esophagus	UBERON:0001976	95.07	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.96	gold quality
placenta	UBERON:0001987	94.91	gold quality
gingiva	UBERON:0001828	94.86	gold quality
squamous epithelium	UBERON:0006914	94.81	gold quality
metanephric glomerulus	UBERON:0004736	94.74	gold quality
amniotic fluid	UBERON:0000173	94.50	gold quality
adult organism	UBERON:0007023	93.86	gold quality
kidney epithelium	UBERON:0004819	93.51	gold quality
parietal pleura	UBERON:0002400	93.16	gold quality
saphenous vein	UBERON:0007318	92.99	gold quality
blood vessel layer	UBERON:0004797	92.43	gold quality
mucosa of stomach	UBERON:0001199	92.26	gold quality
cervix squamous epithelium	UBERON:0006922	92.13	silver quality
metanephros	UBERON:0000081	92.08	gold quality
penis	UBERON:0000989	92.00	gold quality
seminal vesicle	UBERON:0000998	91.94	gold quality
oral cavity	UBERON:0000167	91.87	gold quality
jejunal mucosa	UBERON:0000399	91.86	gold quality
pleura	UBERON:0000977	91.76	gold quality
descending thoracic aorta	UBERON:0002345	91.72	gold quality
endometrium	UBERON:0001295	91.71	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.69	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	32.73
E-GEOD-135922	yes	27.97
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
CCND1	Repression
COL1A1
HNRNPH1
VEGFA	Unknown
VIM

Upstream regulators (CollecTRI, top): AR, ESR1, KDM5B, TBXT, TCF3, TEF, TP53, ZBED1

miRNA regulators (miRDB)

126 targeting HEXIM1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4493	99.90	66.48	977

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 22.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Biochemically characterized a hexamethylene bisacetamide-inducible protein HEXIM1, which is a novel nuclear protein. Interacts with p50 of NF-kB and suppresses NF-kB transcription. (PMID:12581153)
• MAQ1 cooperates with 7SK RNA to form a novel type of CDK inhibitor. (PMID:12832472)
• Binding of the 7SK snRNA turns the HEXIM1 protein into a P-TEFB (CDK9/cyclin T) inhibitor. (PMID:15201869)
• HEXIM1 and HEXIM2 exhibit distinct expression patterns in various human tissues (PMID:15713661)
• utilization of HEXIM1 or HEXIM2 to bind and inhibit P-TEFb can be differentially regulated in vivo. (PMID:15713662)
• Hexim1 has a cyclin T-binding domain and binds competitively to HIV-1 Tat (PMID:15855166)
• increased estrogen down regulated gene 1 expression results in inhibition of cyclin T1 recruitment and estrogen receptor 1 DNA binding (PMID:15940264)
• HEXIM1 forms a transcriptionally abortive complex with glucocorticoid receptor without involving 7SK RNA and positive transcription elongation factor b. (PMID:15941832)
• HEXIM1 dimer associates with only one molecule of RNA. (PMID:15965233)
• HIV-1 Tat transactivation is effectively inhibited by co-expression of HEXIM1; HEXIM1 expression specifically represses transcription mediated by the direct activation of P-TEFb through artificial recruitment of GAL4-CycT1 (PMID:15992410)
• analysis of positive transcription elongation factor - HEXIM1 - 7SK RNA complex (PMID:15994294)
• Ectopic expression of HEXIM1 causes growth inhibition and promotes neuronal differentiation. These findings highlight a crucial role of HEXIM1 protein during cell differentiation. (PMID:16222702)
• the interplay between 7SK snRNA and oppositely charged regions in HEXIM1 direct its binding to P-TEFb and subcellular localization that culminates in the inhibition of transcription (PMID:16362050)
• Binding of HEXIM1 is a prerequisite for association of P-TEFb with the G302-C324 apical region of the 3’ hairpin of 7SK that is highly reminiscent of the human immunodeficiency virus transactivation-responsive RNA. (PMID:16382153)
• Data show that the transcription-dependent dissociation of P-TEFb-HEXIM1-7SK RNA relies upon formation of hnRNP-7SK RNA complexes. (PMID:17709395)
• provide structural insights how Hexim1 recognizes the Cyclin T1 subunit of positive transcription elongation factor b (PMID:17724342)
• a mutant HEXIM1 protein that cannot be phosphorylated and released from P-TEFb and 7SK snRNA via the PI3K/Akt pathway antagonizes this HMBA-mediated induction of viral production. (PMID:17937499)
• NPM binds to HEXIM1 in vitro and in vivo, and functions as a negative regulator of HEXIM1. (PMID:18371977)
• HEXIM1 may act as a gene-selective transcriptional regulator via direct interaction with certain transcriptional regulators including glucocorticoid receptor. (PMID:18407829)
• HEXIM1 regulation on estrogen action showed a decrease in estrogen-stimulated recruitment of ERalpha, P-TEFb, and S2P RNAP II to promoter and coding regions of ERalpha-responsive genes pS2 and CCND1 with increased HEXIM1 expression in MCF-7 cells (PMID:18757415)
• HEXIM1 may participate in tissue-selective determination of glucocorticoid sensitivity via direct interaction with GR at least in certain gene sets including atp1a1 and scnn1a. (PMID:18801933)
• Ubiquitination of HEXIM1 protein increases the inhibitory ability of HEXIM1 protein on P-TEFb-dependent transcription, but does not lead to proteasome-dependent protein degradation of HEXIM1. (PMID:19617712)
• The tripartite protein-RNA complex formation between Hexim, Cyclin T and 7SK snRNA, was analyzed. (PMID:19883659)
• T-loop phosphorylated Cdk9 localizes to nuclear speckle domains which may serve as sites of active P-TEFb function and exchange between the Brd4 and 7SK/HEXIM1 regulatory complexes. (PMID:20201073)
• binding to Cyclin T1 induces an asymmetry or sterical hindrance in the first coiled coil segment of dimeric Hexim1 that disallows formation of a 2:2 complex. (PMID:20210365)
• data provide evidence to suggest a novel role for HEXIM1 in cancer progression (PMID:20453883)
• reincorporation of HEXIM1 into the 7SK snRNP is likely the regulated step of reassembly of the 7SK snRNP containing P-TEFb (PMID:20808803)
• Tat efficiently replaces HEXIM1 on the 7SK snRNA in vivo and it promotes the disassembly of the 7SK/HEXIM/P-TEFb negative transcriptional regulatory snRNP to augment the nuclear level of active P-TEFb. (PMID:20976203)
• Structural insights were provided into the recognition of the regulator protein Hexim1 by P-TEFb and the modulation of coiledcoil dynamics by specific discontinuities. (PMID:22033481)
• Changes in Hexim-1 protein expression and cellular distribution significantly influence androgen receptor activation and transforming growth factor (TGF)-beta signaling in prostate cancer progression. (PMID:22095517)
• N-terminal residues in cyclin T1 are specifically involved in the binding of cyclin T1 to HEXIM1 but not to Tat. (PMID:22342181)
• results not only identify HEXIM1 as a positive regulator of p53, but also propose a novel molecular mechanism of p53 activation caused by the anti-cancer drugs and compounds. (PMID:22948151)
• P-TEFb/HEXIM1-dependent transcriptional regulation may play a pathophysiological role in RVH and be a novel therapeutic target for mitigating RVH in PAH (PMID:23300697)
• This study demonstrates a novel role of HEXIM1 in regulating human pluripotent stem cells fate through a P-TEFb-independent pathway. (PMID:23977357)
• There is evidence for a direct interaction between HIF-1alpha and HEXIM1, and HEXIM1 up-regulated hydroxylation of HIF-1alpha. (PMID:24015760)
• the release of P-TEFb from the 7SK snRNP led to increased synthesis of HEXIM1 but not HEXIM2 (PMID:24515107)
• HEXIM1 functions as an AR (androgen receptor) co-repressor as it physically interacts with the AR and is required for the ability of anti-androgens to inhibit androgen-induced target gene expression and cell proliferation. (PMID:24844355)
• Data indicate the binding of RNA-binding protein HEXIM with 7SKsnRNP complex comprising the non-coding RNA 7SK and proteins MePCE and LARP7. (PMID:25863285)
• PPM1G phosphatase directly binds 7SK RNA and the kinase inhibitor Hexim1 once P-TEFb has been released from the 7SK snRNP. (PMID:26324325)
• Suggest that greater tumor associated macrophage density, strong Hexim1 expression, strong SMAD2 expression, and mild SMAD7 expression play important roles in the progression of prostate adenocarcinoma. (PMID:26608417)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	hexim1	ENSDARG00000036482
mus_musculus	Hexim1	ENSMUSG00000048878
rattus_norvegicus	Hexim1	ENSRNOG00000003203
drosophila_melanogaster	Hexim	FBGN0038251

Paralogs (1): HEXIM2 (ENSG00000168517)

Protein

Protein identifiers

Protein HEXIM1 — O94992 (reviewed: O94992)

Alternative names: Cardiac lineage protein 1, Estrogen down-regulated gene 1 protein, Hexamethylene bis-acetamide-inducible protein 1, Menage a quatre protein 1

All UniProt accessions (1): O94992

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional regulator which functions as a general RNA polymerase II transcription inhibitor. Core component of the 7SK RNP complex: in cooperation with 7SK snRNA sequesters P-TEFb in a large inactive 7SK snRNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation. May also regulate NF-kappa-B, ESR1, NR3C1 and CIITA-dependent transcriptional activity. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway.

Subunit / interactions. Homooligomer and heterooligomer with HEXIM2; probably dimeric. Core component of the 7SK RNP complex, at least composed of 7SK RNA, LARP7, MEPCE, HEXIM1 (or HEXIM2) and P-TEFb (composed of CDK9 and CCNT1/cyclin-T1). Interacts with the N-CoR complex through NCOR1. Interacts with ESR1 and NR3C1. May interact with NF-kappa-B through RELA. Interacts with CCNT2; mediates formation of a tripartite complex with KPNA2. Part of the HDP-RNP complex composed of at least HEXIM1, PRKDC, XRCC5, XRCC6, paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATR3) and NEAT1 non-coding RNA.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Ubiquitously expressed with higher expression in placenta. HEXIM1 and HEXIM2 are differentially expressed. Expressed in endocrine tissues.

Domain organisation. The coiled-coil domain mediates oligomerization.

Induction. Up-regulated by HMBA (hexamethylene bisacetamide) (at protein level). Down-regulated by estrogen.

Miscellaneous. Inhibits Tat activity which is required for HIV-1 transcription.

Similarity. Belongs to the HEXIM family.

RefSeq proteins (1): NP_006451* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024872	HEXIM	Family

Pfam: PF15313

UniProt features (34 total): mutagenesis site 10, region of interest 7, modified residue 7, compositionally biased region 5, helix 3, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3S9G	X-RAY DIFFRACTION	2.1
2GD7	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94992-F1	67.26	0.28

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (7): 97, 98, 233, 236, 237, 252, 260

Mutagenesis-validated functional residues (10):

Position	Phenotype
152–155	abolishes interaction with 7sk snrna.
154–156	abolishes interaction with 7sk snrna.
203	abolishes interaction with p-tefb; when associated with d-205.
205	abolishes interaction with p-tefb. same effect; when associated with d-203.
208	partial loss of function.
271	loss of function.
287	loss of oligomerization; when associated with a-294; a-332 and a-339. loss of function and interaction with p-tefb; when
294	loss of oligomerization; when associated with a-287; a-332 and a-339. loss of function and interaction with p-tefb; when
332	loss of oligomerization; when associated with a-287; a-294 and a-339.
339	loss of oligomerization; when associated with a-287; a-294 and a-332.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 327 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, BROWNE_HCMV_INFECTION_4HR_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_POSITIVE_REGULATION_OF_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, DAZARD_RESPONSE_TO_UV_SCC_UP, DAUER_STAT3_TARGETS_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_UP, GOBP_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR

GO Biological Process (9): negative regulation of transcription by RNA polymerase II (GO:0000122), activation of innate immune response (GO:0002218), heart development (GO:0007507), negative regulation of viral transcription (GO:0032897), negative regulation of transcription elongation by RNA polymerase II (GO:0034244), innate immune response (GO:0045087), positive regulation of signal transduction by p53 class mediator (GO:1901798), immune system process (GO:0002376), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (8): protein kinase inhibitor activity (GO:0004860), cyclin-dependent protein serine/threonine kinase inhibitor activity (GO:0004861), snRNA binding (GO:0017069), identical protein binding (GO:0042802), 7SK snRNA binding (GO:0097322), P-TEFb complex binding (GO:0106140), transcription regulator inhibitor activity (GO:0140416), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), 7SK snRNP (GO:0120259)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
activation of immune response	1
positive regulation of innate immune response	1
animal organ development	1
circulatory system development	1
viral transcription	1
regulation of viral transcription	1
negative regulation of viral process	1
transcription elongation by RNA polymerase II	1
negative regulation of DNA-templated transcription, elongation	1
regulation of transcription elongation by RNA polymerase II	1
immune response	1
defense response to symbiont	1
signal transduction by p53 class mediator	1
regulation of signal transduction by p53 class mediator	1
positive regulation of intracellular signal transduction	1
biological_process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
protein kinase activity	1
kinase inhibitor activity	1
protein kinase regulator activity	1
cyclin-dependent protein serine/threonine kinase activity	1
cyclin-dependent protein serine/threonine kinase regulator activity	1
protein serine/threonine kinase inhibitor activity	1
RNA binding	1
protein binding	1
snRNA binding	1
protein-containing complex binding	1
regulation of gene expression	1
transcription regulator activity	1
molecular function inhibitor activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2392 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HEXIM1	CCNT1	O60563	999
HEXIM1	MEPCE	Q7L2J0	999
HEXIM1	LARP7	Q4G0J3	999
HEXIM1	CDK9	P50750	998
HEXIM1	CCNT2	O60583	972
HEXIM1	HEXIM2	Q96MH2	968
HEXIM1	BRD4	O60885	966
HEXIM1	BCL11B	Q9C0K0	918
HEXIM1	PPM1G	O15355	881
HEXIM1	RBM8A	Q9Y5S9	873
HEXIM1	HTATSF1	O43719	801
HEXIM1	SART3	Q15020	787
HEXIM1	AFF1	P51825	721
HEXIM1	NCOR1	O75376	699
HEXIM1	POLR2A	P24928	695

IntAct

112 interactions, top by confidence:

A	B	Type	Score
CDK9	CCNT1	psi-mi:“MI:0914”(association)	0.980
HEXIM1	CDK9	psi-mi:“MI:0914”(association)	0.940
CDK9	HEXIM1	psi-mi:“MI:0915”(physical association)	0.940
HEXIM1	CCNT1	psi-mi:“MI:0407”(direct interaction)	0.930
HEXIM1	CCNT1	psi-mi:“MI:0915”(physical association)	0.930
CCNT1	HEXIM1	psi-mi:“MI:0407”(direct interaction)	0.930
HEXIM1	CCNT1	psi-mi:“MI:0914”(association)	0.930
CCNT1	HEXIM1	psi-mi:“MI:0914”(association)	0.930
HEXIM1	LARP7	psi-mi:“MI:0915”(physical association)	0.920
LARP7	CCNT1	psi-mi:“MI:0914”(association)	0.850
HEXIM1	HEXIM2	psi-mi:“MI:0915”(physical association)	0.800
tat	CCNT1	psi-mi:“MI:0914”(association)	0.780
VPS29	VPS26C	psi-mi:“MI:0914”(association)	0.760
AFF4	ELL2	psi-mi:“MI:0914”(association)	0.730
CDK9	AIP	psi-mi:“MI:0914”(association)	0.730

BioGRID (1109): HEXIM1 (Affinity Capture-RNA), HEXIM1 (Affinity Capture-RNA), HEXIM1 (Affinity Capture-RNA), HEXIM1 (Affinity Capture-MS), LARP7 (Affinity Capture-MS), CDK9 (Affinity Capture-MS), OSBPL1A (Affinity Capture-MS), UBE2O (Affinity Capture-MS), MEPCE (Affinity Capture-MS), CSNK2A2 (Affinity Capture-MS), CSNK2A1 (Affinity Capture-MS), EEF1A2 (Affinity Capture-MS), HEXIM2 (Affinity Capture-MS), CSNK2B (Affinity Capture-MS), CCNT2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GUX5, A2AHC3, A2AIW0, A2CE83, A5D8S8, A5WUN7, E2QSX5, F1R983, O94992, P28290, P46414, P46527, P46529, P61406, Q08DX0, Q0X0C4, Q13009, Q13111, Q28GJ0, Q2KJD6, Q3UHU5, Q4V7W3, Q502L1, Q503Y8, Q5M9G1, Q5RAK6, Q5SXA9, Q5T5Y3, Q5U3H9, Q60439, Q60610, Q60664, Q62627, Q640U0, Q641E3, Q6NXJ0, Q6PCQ0, Q6RFY2, Q6WCQ1, Q6ZMN7

Diamond homologs: A5D8S8, O94992, Q0X0C4, Q0X0E2, Q3TVI4, Q4V7W3, Q5M9G1, Q8R409, Q96MH2

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
NPM1	“down-regulates activity”	HEXIM1	binding
HEXIM1	“down-regulates activity”	P-TEFb	binding
LARP7	“down-regulates activity”	HEXIM1	binding
HEXIM1	“up-regulates activity”	KDM5B	relocalization
MDM2	“up-regulates activity”	HEXIM1	ubiquitination
CDK1	“down-regulates activity”	HEXIM1	phosphorylation
HNRNPU	“up-regulates quantity by stabilization”	HEXIM1	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 102 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of RNA Pol II elongation complex	5	15.4×	2e-03
RNA Polymerase II Transcription Elongation	5	15.4×	2e-03
TP53 Regulates Transcription of DNA Repair Genes	5	14.4×	2e-03
RNA Polymerase II Pre-transcription Events	5	10.9×	4e-03
Regulation of PLK1 Activity at G2/M Transition	5	10.1×	5e-03
SRP-dependent cotranslational protein targeting to membrane	6	9.5×	2e-03
mRNA Splicing	5	8.7×	8e-03
Major pathway of rRNA processing in the nucleolus and cytosol	7	6.9×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription elongation by RNA polymerase II	5	17.7×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

38 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

175 predictions. Top by Δscore:

Variant	Effect	Δscore
17:45148625:G:T	donor_gain	0.9800
17:45148625:GGAGA:G	donor_gain	0.9700
17:45148626:GAGA:G	donor_gain	0.9700
17:45148629:A:G	donor_gain	0.9700
17:45148654:GC:G	donor_gain	0.9500
17:45148633:G:GG	donor_gain	0.8900
17:45148516:A:T	donor_gain	0.8500
17:45148632:A:AG	donor_gain	0.8500
17:45148535:G:GT	donor_gain	0.8100
17:45149324:G:GG	donor_gain	0.8000
17:45148688:TGG:T	donor_gain	0.7900
17:45148649:C:G	donor_gain	0.7600
17:45148628:GATGA:G	donor_gain	0.7300
17:45148672:G:T	donor_gain	0.7300
17:45148655:C:G	donor_gain	0.7200
17:45149323:A:AG	donor_gain	0.7200
17:45148806:T:TA	donor_gain	0.7100
17:45148807:A:AA	donor_gain	0.7100
17:45148515:G:T	donor_gain	0.7000
17:45148705:G:GT	donor_gain	0.6900
17:45148678:G:GT	donor_gain	0.6800
17:45148629:A:AG	donor_gain	0.6700
17:45148503:C:T	donor_gain	0.6600
17:45148550:G:T	donor_gain	0.6500
17:45148715:G:GT	donor_gain	0.6500
17:45149175:G:T	acceptor_gain	0.6500
17:45148624:G:GT	donor_gain	0.6400
17:45148628:GA:G	donor_gain	0.6400
17:45148635:T:A	donor_gain	0.6100
17:45149319:GGACA:G	donor_gain	0.6100

AlphaMissense

2354 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:45149802:C:A	N204K	1.000
17:45149802:C:G	N204K	1.000
17:45149812:T:C	F208L	1.000
17:45149813:T:C	F208S	1.000
17:45149813:T:G	F208C	1.000
17:45149814:C:A	F208L	1.000
17:45149814:C:G	F208L	1.000
17:45149989:T:C	F267L	1.000
17:45149991:C:A	F267L	1.000
17:45149991:C:G	F267L	1.000
17:45150050:T:C	L287P	1.000
17:45149792:C:A	A201E	0.999
17:45149795:C:A	P202H	0.999
17:45149800:A:G	N204D	0.999
17:45149804:C:T	T205I	0.999
17:45149812:T:G	F208V	0.999
17:45149816:T:A	L209H	0.999
17:45149816:T:C	L209P	0.999
17:45149819:T:C	M210T	0.999
17:45149974:T:C	F262L	0.999
17:45149976:T:A	F262L	0.999
17:45149976:T:G	F262L	0.999
17:45149990:T:C	F267S	0.999
17:45149990:T:G	F267C	0.999
17:45150026:T:C	L279P	0.999
17:45150042:G:C	K284N	0.999
17:45150042:G:T	K284N	0.999
17:45150050:T:A	L287H	0.999
17:45150071:T:C	L294P	0.999
17:45150083:T:C	L298P	0.999

dbSNP variants (sampled 300 via entrez): RS1000517328 (17:45148614 C>G,T), RS1000524639 (17:45150713 G>A), RS1001029919 (17:45150899 C>A), RS1001708235 (17:45148135 A>T), RS1001735440 (17:45150305 C>T), RS1002566249 (17:45151189 G>C), RS1003348286 (17:45148731 T>C), RS1003372373 (17:45146931 T>G), RS1003383720 (17:45146615 G>C), RS1003576689 (17:45152492 C>T), RS1004653392 (17:45149022 A>G), RS1004759032 (17:45150997 C>T), RS1005197225 (17:45148846 T>G), RS1005227699 (17:45146902 T>C), RS1005322401 (17:45146498 C>G,T)

Disease associations

OMIM: gene MIM:607328 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000395_1	Systolic blood pressure	1.000000e-08
GCST003043_195	Inflammatory bowel disease	2.000000e-06
GCST003045_58	Ulcerative colitis	6.000000e-08
GCST004412_12	Craniofacial microsomia	9.000000e-06
GCST006661_255	Male-pattern baldness	2.000000e-22
GCST008916_39	Asthma	8.000000e-12
GCST009798_36	Asthma	2.000000e-10
GCST010097_17	Insomnia	1.000000e-10
GCST010703_91	Brain morphology (MOSTest)	2.000000e-65
GCST90000025_591	Appendicular lean mass	1.000000e-52

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0004346	neuroimaging measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3120044 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	increases expression, decreases reaction	15
Valproic Acid	affects expression, decreases expression, increases expression	4
Cyclosporine	decreases expression	3
OTX015	increases expression	2
sodium arsenite	increases abundance, increases expression, affects cotreatment, decreases expression	2
Acetaminophen	increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Cisplatin	increases expression	2
Tretinoin	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
mivebresib	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	increases expression, affects cotreatment	1
periodate-oxidized adenosine	affects expression	1
epigallocatechin gallate	increases expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
nutlin 3	increases secretion, affects cotreatment	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
quizartinib	decreases reaction, increases expression	1
GSK1210151A	increases expression	1
Leflunomide	decreases expression	1
Amiodarone	increases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3122275	Binding	Induction of HEXIM1 protein expression in human LNCAP cells at 500 uM after 24 hrs by Western blotting analysis relative to control	Lead optimization of HMBA to develop potent HEXIM1 inducers. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.